ES2501142T3 - Device to examine an internal body cavity - Google Patents

Abstract

A system for indicating the transferability of a target device, live, non-degradable, through a GI tract, so that the system comprises: - a target device, live, non-degradable; - a live device (50), comprising: - a soluble body (58); - a soluble cover (58 '), fixed to the body (58), such that said body (58) and said cover (58') define a closed receptacle; - an outer covering (54), which is essentially impervious to liquids from the GI tract, which encloses the cover (58 ') and the body (58) with the exception of a window (56), such that said coating ( 54) covers less than the entire cover (58 '), so that the cover (58') is not covered in the window (56); and - a passive monitoring device (53), said device having live (50) initial dimensions similar to the dimensions of the target device, live, non-degradable, such that the body (58) is made of a material which is faster to dissolve than the lid material (58 '); and in which the dissolution rate of the lid (58 '), once it has come into contact with the liquids of the GI tract, depends on window size parameters (56), the properties of the lid material ( 58 ') and the thickness of the lid (58'), so that a predetermined period of time, after which the lid (58 ') will dissolve sufficiently to create an opening through the window (56), through which liquids from the GI tract come into contact with the body (58), it depends on the material and the thickness of the lid (58 ') as well as the size of the window (56), so that the lid ( 58 ') is of such material and thickness, and the window (56) is of such a size, that the body (58) and the lid (58') dissolve in the liquids of the GI tract at such a speed, that : - the live device (50) has its initial dimensions during the period of contact time with the liquids of the GI tract; and - after the predetermined period of contact with the liquids of the GI tract, the dimensions of said live device (50) are reduced to final dimensions that are smaller than the initial dimensions; and - an external inductor for inducing said monitoring device (53) to send a signal.

Description

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DESCRIPTION

Device to examine an internal body cavity

Field of the Invention

The present invention relates to a system for examining an internal body cavity. The system is useful, among other things, to detect anomalies in the configuration of an internal cavity.

Background of the invention

The tubular organs of the human body can have a convolute cavity configuration. The gastrointestinal tract, for example, begins in the oral cavity and continues through the esophagus, stomach, duodenum and small intestine, which is a long tube that folds many times to fit inside the abdomen. The small intestine is attached to the large intestine, which begins in the cecum, a small cavity turned out and shaped like a sac, and then continues through the ascending colon, the transverse colon, the descending colon and the sigma (S-shaped ) or pelvic colon, to the rectum. These internal body cavities may suffer pathologies that may affect the anatomy or configuration of the internal cavity. For example, the strictures, narrowing or closing of an internal cavity of normal configuration, can be caused by calcification

or by the presence of scar tissue or a tumor. The strictures of the esophagus are a common complication of gastroesophageal reflux disease (GERD - "chronic gastro-esophageal reflux disease" -). An acute, complete obstruction of the esophagus can occur when the food is lodged within the esophageal stricture. Endoscopy is usually used to recover food and release the obstruction.

Various procedures are available to stretch (dilate) the strictures without resorting to surgery. These involve the placement of a balloon or dilator through strictness in the course of an endoscopy procedure.

The methods for diagnosing internal body cavities are usually related to the symptoms or are invasive. Non-invasive diagnostic techniques of the gastrointestinal tract (GI - "gastrointestinal" -) include the use of autonomous, swallowable and non-degradable solid capsules, electronically or magnetically labeled. These autonomous capsules include capsules for measuring motility in the GI tract, gastric pH (such as the Heidelberg capsule) and live temperature (such as the CoreTempTM capsule). Gastric transit can also be measured by using a biomagnetic measuring device, such as a magnetically labeled capsule, which consists of a solid and non-degradable oral dose form containing magnetite powder encapsulated in silicone rubber (W. Weitschies , R. Kotitz, D. Cordin, L. Trahms (1997), J. Pharm. Sci. 86: 1218-1222). Such capsules are usually driven through the GI system by peristaltic movements. These non-invasive methods allow reaching parts of the intestine, especially distal, or more distant, parts of the small intestine (jejunum and ileum) that cannot be reached by other methods. However, in rare cases of various strictures of the GI tract, swallowing a solid bolus (such as an electronically or magnetically labeled capsule) may cause obstruction of the GI tract.

Also, medication delivery devices consisting of non-degradable solid boluses can often be swallowed. Medication delivery devices may include controlled diffusion systems or environment sensitive systems. In these systems, there may be a combination of polymer matrices and biodegradable agents (usually medications) that allow a drug to diffuse through the pores or macromolecular structure of the polymer when the system is introduced live. In some cases, the devices are swelling controlled release systems that are based on hydrogels. Hydrogels are polymers that will swell without dissolving when placed in water or other biological fluids. In this way, swelling-controlled systems are initially dry, so that, when placed inside the body, they will absorb fluids and swell. The swelling increases the mesh size of the polymer, which allows the medicine to diffuse through the swollen network, into the external environment. These systems are usually essentially stable in a live environment and are not modified in size due to swelling or degradation. Swallowing these systems can, in this way, in cases of strictures in the GI tract, cause obstruction of the GI tract.

One such system has been disclosed in US 5,004,614 A, which discloses a controlled release device having an active agent core and an outer coating, which is impervious to the release of the active agent as well as to the entrance of environment fluids. A hole made in the outer coating allows controlled release of the active agent, in order to allow substantially all of the active agent to be released through the hole.

Non-invasive methods of detecting strictures, specifically in the GI tract, usually include series of X-rays that are based on the introduction of an opaque material to X-rays (radiopaque) (barium, gastrographin or others). The material resides for some time on the walls of the GI tract, which makes it possible to examine the X-ray images of the GI tract: This technique has several disadvantages, namely a low detection rate and exposure to radiation from rays. X.

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Live devices, pills or other medical systems may require passage through the GI tract. However, it can be difficult to predict whether such devices, pills or systems can achieve a safe passage through the GI tract without really trying to get objects through the tract.

Consequently, there is a need for an efficient and low-risk method to examine an internal body cavity. Specifically, there is a need for a safe and high-performance method to detect abnormalities in an internal body cavity, such as abnormal motility in the GI tract, strictures or other configuration abnormalities in the internal body cavities. There is also a need to determine if objects of a certain size and / or shape can pass safely through the GI tract.

Compendium of the invention

The invention is defined by the subject matter of claim 1.

According to one embodiment, the initial dimensions may be a diameter of approximately 11 mm, and the reduced dimensions may be a diameter between approximately 2 m and approximately 10 m. Other dimensions are possible.

According to another embodiment, the monitoring device actively emits signals, such as electromagnetic or acoustic signals. According to yet another additional embodiment, the device includes a label, such as a radioactive material, magnetized particles or a radiopaque material. These tags can be detected, for example, by a radioactive emission detector, a magnetometer or an X-ray machine. According to yet another embodiment, the device includes a marker, such as a pigment.

According to the invention, a body cavity can be investigated using a device comprising a soluble body, a soluble lid fixed to the body, such that the body and the lid define a closed receptacle, and an essentially impermeable outer liner that encloses The lid and the body. The lining covers less than the entire lid. The device according to an embodiment of the invention may contain a label, an RFID [radio frequency identification], a marker or any substance enclosed within the closed receptacle. In accordance with the invention, after the predetermined period of time has elapsed, the body and the lid dissolve and the outer coating is emptied.

According to still other embodiments, the method may also include detecting at least one parameter of the internal body cavity, such as pH, pressure and temperature. According to one embodiment, data of the detected parameter can be transmitted to an external receiving system.

In accordance with a further embodiment of the invention, a live imaging device is further provided comprising an image sensor, a lighting source, an internal power source and an electronic ID tag. The imaging device may also include a transmitter to transmit image data to an external receiving system.

Brief description of the drawings

The present invention will be more fully understood and appreciated by the following detailed description, taken in combination with the drawings, in which:

Figure 1A is a schematic illustration of the two phases of a live examination device, in accordance with an embodiment of the invention;

Figure 1B is a schematic illustration of the two phases of a live examination device, in accordance with another embodiment of the invention;

Figure 2A is a schematic cross-sectional illustration of an examination device having a coating and a padding, in accordance with an embodiment of the invention;

Figure 2B is a schematic side view illustration of an examination device having a liner and a padding, in accordance with another embodiment of the invention;

Figure 2C is a graph illustrating the step function followed by the examination device according to an embodiment of the invention;

Figure 3A is a schematic illustration of an examination device comprising a monitoring device according to an embodiment of the invention;

Figure 3B is a schematic illustration of a monitoring system according to an embodiment of the invention;

Figure 3C is a cross-sectional and schematic illustration of an examination device capable of being traced, in accordance with another embodiment of the invention;

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Figure 3D is a schematic illustration of a monitoring system according to another embodiment of the invention; Y

Figure 4 is a schematic illustration of an examination device according to an embodiment of the invention.

Detailed description of the invention

Various aspects of the present invention will be described in the following description. For the purposes of the explanation, specific configurations and details are set forth in order to provide a thorough understanding of the present invention. However, it will also be apparent to a person skilled in the art that the present invention can be practiced without the specific details presented herein. On the other hand, well-known features may have been omitted or simplified in order not to obscure the present invention. The methods described herein are not part of the claimed invention.

An atypical passage of an object through an internal body cavity, or symptoms that appear after the insertion of an object into an internal body cavity, may be indicative of an abnormal configuration of the internal body cavity. An examination device according to embodiments of the invention, which can examine an internal body cavity and may be an indicator of the configuration of the internal body cavity, is designed to be safely evacuated from the body, regardless of the configuration of The internal body cavity.

According to an embodiment of the invention, a device comprises a coating and a filling. The coating has initial dimensions that are modifiable to final dimensions, and the filling comprises particles that are of the final dimensions. The final dimensions allow the device to pass through an internal body cavity configuration, which is not allowed by the initial dimensions.

In a predetermined time, a predetermined pressure, produced internally to the device, is exerted on the coating. The default pressure causes the coating to break or crush. In this way, in a predetermined time, the device is degraded or reduced, essentially in a stepped manner, to dimensions that allow the device to pass inside a configuration of internal body cavity, which is not allowed by the initial dimensions.

The predetermined pressure is usually different from the endoluminal pressure, or internal to the internal cavity, which normally reigns. The predetermined time is a period longer than the period of time it usually takes for the device to pass through an internal body cavity with a normal configuration.

The initial dimensions are usually determined according to the known anatomy and / or physiology of an internal body cavity. In its final phase, the dimensions of the examination device are usually smaller and its shape has possibly changed in such a way that it can pass freely through the internal body cavity even if the dimensions of the cavity are less than expected according to the known anatomy and / or physiology of the internal body cavity.

The prosecution from an initial phase to a final phase of the examination device, namely, by producing a predetermined pressure within the device, can, for example, be favored by the conditions inside the internal cavity or can be externally controlled. . It should be appreciated that the device progresses, usually, from an initial phase to a final phase, for example, experiencing a change in its dimensions, when the predetermined pressure is exerted on the device liner. The predetermined pressure is usually produced within the device and exerted on the coating of the device live. It is therefore conceivable that a device according to an embodiment of the invention remains in its initial phase indefinitely. For example, if the device is not inserted live, or if the device is inserted live but is evacuated from the body within a period of time that is shorter than the predetermined time, the predetermined pressure within the device will not occur and The device will not experience any change in dimensions.

The examination device may additionally comprise a monitoring mechanism, such as a radioactive, color or magnetic tag or an electronic ID tag (for example, an RFID tag). Other monitoring mechanisms may be used. An external operator, who can usually be aware of the phase in which the device is at a given time (as will be detailed below), can therefore follow the progression of the device through of the internal body cavity. Additionally, the device may also comprise an examination mechanism, such as a thermometer or a pH meter, to examine the conditions inside the internal cavity, or other sensing devices such as an imaging device.

In one embodiment of the invention, the test device is a test device that comprises initial dimensions that will allow free passage of the test device through the internal body cavity with a normal configuration, but which will not allow the free passage of the device. Assay through certain constricted or otherwise narrowed internal body cavities, or an abnormal configuration. In its phase 4 10

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In the end, the size of the test device is usually smaller and its shape has been modified, possibly, in such a way that it can pass freely through the internal body cavity, even if the internal cavity has a configuration abnormal.

In another embodiment of the invention, the test device can be used to simulate the passage of a live device, such as a diagnostic and / or therapeutic device, through an internal body cavity. In this case, it may be advantageous to obtain information on the passage of the test device through the internal body cavity, when designing a specific live device or determining whether a certain live device can be used safely in a patient. In one embodiment, test devices sized and shaped differently according to an embodiment of the invention can be passed through an internal body cavity to determine the most suitable size and shape for a live device to be passed freely and safely through this same internal body cavity. In another embodiment, the test device comprises at least two phases: an initial phase in which the dimensions of the test device resemble approximately the dimensions of a live target device, and a final phase in which the dimensions of the test device Test device are modified in order to make it possible for the test device to pass through certain abnormally configured internal body cavities. The passage of the test device through an internal body cavity simulates the passage of the target live device through the internal body cavity and, therefore, a safe method of indication with respect to the susceptibility of device transfer is provided. live target inside the internal body cavity.

In the method according to an embodiment of the invention, an examination device can examine the conditions inside the internal cavity, or test the configuration of an internal body cavity, detect configuration anomalies in an internal body cavity and / or simulate the passage of a live device into an internal body cavity without running any danger of long-term obstruction of the internal body cavity. An examination device according to an embodiment of the invention, in its initial phase, comprises dimensions such that it can usually pass through an internal body cavity and / or provide a good approximation of the passage of a live device inside the internal body cavity. In its final phase, the dimensions of the examination device can be modified (usually reduced, although other changes are contemplated) so that it can pass through an internal body cavity of abnormal configuration, while the device of examination could not do it in its initial phase as a result of its dimensions.

In the event that the internal body cavity is of unexpected dimensions (the expected dimensions being based, for example, on the known or typical anatomy and / or on the physiology of the internal body cavity), or in the case that there is a strictness or any other anomaly of configuration in the internal body cavity, the examination device, with its initial dimensions, may be prevented from continuing its typical or expected passage inside the internal body cavity. After a predetermined time, the dimensions of the examination device can be modified in such a way that the test device, in its final phase, usually in a degraded or reduced form, will not be blocked in its passage, even at through a smaller or abnormally shaped internal body cavity.

If no clinical or configuration abnormality is present in the internal body cavity, the passage of the test device through the internal body cavity will be the usual one, and the examination device will pass through the internal body cavity and leave the body while still having its initial dimensions. However, in case the internal body cavity has an abnormal configuration (for example, there is a strictness), or if there is a clinical problem (for example, slow or no motility at all in the GI tract), the device Exam is held in the internal body cavity and reaches its final dimensions while in the internal body cavity. The degraded or reduced device is able to continue its passage through the internal body cavity until finally leaving the body. It will be appreciated, therefore, that the device and the method of the invention can be used to detect clinical and / or configuration abnormalities in internal body cavities through which the device can be passed and from which it can be evacuated, such as the GI tract, the urogenital tract, the reproductive tract, the oral-nasal cavity, etc., or in a portion of any of these internal cavities.

A person skilled in the art can easily adjust the specific design of the examination device and the predetermined period of time between initial and final phases of the examination device so that it is applicable to a specific internal body cavity having a known anatomy and physiology. .

Figures 1A and 1B are schematic illustrations of an embodiment of the invention. Referring to Figures 1A and 1B, an examination device 10, having initial dimensions, is inserted into an internal body cavity 100 and is displaced through the internal body cavity 100 (in the direction indicated by arrow A) , either active, or passively. The device 10, which has a diameter of, for example, 1-12 mm, can freely pass through the internal cavity 10, which extends in a width of, for example, between 1 mm and 10 mm, until it reaches to a constraint 101. In the constraint 101, there is only one residual internal cavity in operation of, for example, between about 2 µm and 10 µm. The device (now illustrated in dashed line and referred to with the number 10 ') is unable to proceed with its passage through the internal body cavity 100 due to its dimensions, which are larger than the dimensions of the internal cavity body in the strict 101. The device 10, with its initial dimensions, is therefore locked in the 5 10

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strictness 101.

After a predetermined time, the dimensions of the device 10 are modified. The device 10 can be, for example, crushed or disintegrated, resulting in its final dimensions 12 (in Figure 1A), or broken or degraded, resulting in its final dimensions 14 (in Figure 1B). In its final dimensions 12, the device usually has a reduced volume and a flattened shape, and its diameter is not larger than, for example, between 2 µm and 10 µm. In its final dimensions 14, the device will be, for example, degraded into several fragments or small particles, each of which is not more than, for example, 2 µm wide. The device, in its final dimensions, either 12 or 14, can pass through the constraint 101 and can, for example, be evacuated from the body. In alternative embodiments, the dimensions or shape of the internal body cavity 100 may be different and the device 10 may be modified in other ways, to other dimensions or shapes. For example, it is not necessary for the device to break into more than one fragment.

 Examination device 10 may have been shaped, for example, in capsule form, similar to the swallowable capsule described in US Patent No. 5,604,531, to Iddan (which is incorporated herein by reference), or similar in form and size to the other pills, tablets, capsules and similar elements known in the art.

In one embodiment, a test device shaped as a capsule and having initial dimensions of approximately 11 mm x 26 mm can be used to study the GI tract. The device is swallowed and passively displaced through the GI tract as a result of peristaltic movements of the GI tract, until it is naturally excreted from the body. In the event that the device is not able to move beyond a certain place due to the configuration of the internal body cavity in that place, the device will remain in that place and will degrade after a predetermined time. Once the device has degraded or reduced, for example, as shown in Figures 1A and 1B, it will be excreted naturally from the internal body cavity.

Also, in one embodiment, a powerful magnet can be used from outside the body to move a charged device into the internal body cavity. In the event that the external operator is not able to move the device beyond a certain place as a result of the configuration of the internal cavity in that place, the device can be left in that place so that it will degrade after a predetermined period of time. Once the device has degraded or reduced, for example, as shown in Figures 1A and 1B, it is capable of passively and naturally exiting the internal body cavity.

In another embodiment, the device 10 may have been shaped or sized to resemble an objective diagnostic or therapeutic device that is desired to pass through the patient's internal body cavity, for example, a swallowable imaging device intended for Obtaining images of the GI tract. The device 10 can be safely passed through the GI tract in order to study transferability,

or ability to pass such a device through the GI tract, while its progression can be monitored and / or it is possible to detect the phase in which the device is located (as will be detailed further below). In the event that the device cannot pass through a section of the internal cavity, its shape or dimensions can be modified to allow its passage.

Test devices according to various embodiments of the invention are illustrated in Figures 2A and 2B, although other embodiments of devices having other shapes, dimensions and structures can also be used. According to an embodiment of the invention, a test device is made of an outer coating and an inner filling. The test devices for the GI tract, for example, may initially have an outer sheath and an internal padding, each of them, for example, a few m to a few mm thick. Typically, the outer coating is a thinner layer than the inner padding. According to some embodiments, the outer coating has been designed to confer mechanical resistance to the device and maintain the constant shape and dimensions of the device throughout the initial phase of the device. The coating also serves as a barrier between the internal padding and the environment, such as the interior environment to the internal cavity. The coating usually consists of a layer or a plurality of layers of a material or combination of impervious or slightly permeable materials, which is essentially durable (i.e. it does not corrode or disintegrate) under live conditions. The internal filling, which, in one embodiment, may consist of one or more layers or a suspension of a liquid or gas, usually constitutes small particles or molecules and may produce a pressure within the device when serving, for example, as a source or sink of ions. The filler may also contain adhesives and fillers to, for example, additionally provide mechanical stability to the device.

Referring to Figure 2A, the test device 20 according to one embodiment comprises an outer covering 24 and an inner filling 22. The outer covering 24 consists of a layer of a strong and slightly permeable material that encapsulates the inner filling 22 and controls the diffusion rate of substances from inside the device and / or from outside (for example, the environment of the internal body cavity) to the inside of the device. The internal filling 22 maintains an osmosis that favors the diffusion in and out of ions, so that the internal filling will swell or empty (and be exchanged for fluids from the inner cavity) in a process that will be determined, preferably, due to the filling properties

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internal 22 and whose speed will be limited, preferably, by the properties of the outer coating 24.

In one embodiment, the outer coating 24 may be made of a hydrogel polymer coated with parylene c, such as ethyl cellulose acetate, and the inner filler 22 may be made of filler material, preferably, a biodegradable polymer, such as a polymer of lactide and golicolide (PLGA). In alternative embodiments, other materials may be used. Parylene c, which is a poly (p-xylene) dimer with the replacement of a single chlorine molecule, provides a combination of properties such as low permeability to moisture, chemicals and other corrosive gases. The hydrogel polymer creates a matrix that contains the filler material and is strong enough to withstand the endoluminal pressure, or inside the internal cavity. The filler material absorbs liquid from the environment of the internal body cavity, which oozes through the hydrogel matrix at a rate that is usually determined by the osmotic gradient between the interior environment to the internal cavity and the internal filling , and by properties of the parylene coating c and of the hydrogel polymer such as the extension of the cross-links of the hydrogel polymer, its concentration, its thickness and others.

The filling material swells and, after a certain period of time, begins to press against the outer lining 24. The internal pressure rises as more liquid is absorbed. When the pressure reaches a certain predetermined value, the hydrogel matrix and the parylene coating c are broken and the device 20 is divided into smaller pieces and particles.

In another embodiment, the outer coating 24 may be a low solubility material that is permissible to flow into liquids from inside the internal cavity, or a soluble material that is initially impervious to liquids from inside the internal cavity but which becomes permeable as it dissolves, due to the thickening of the layer. The flow into the liquids inside the internal cavity causes the pressure inside the device 20 to rise and, ultimately, the outer liner 24 is broken, thereby decreasing the dimensions of the device 20.

For example, in a device having a diameter of 11 mm, a layer of parylene c a few µm thick (5 µm to 20 µm) can be used as the outer coating 24, and a filling of 11 mm thick of any suitable filler material. The thickness of the outer coating layer serves to regulate the speed of flow into the inner liquids into the inner cavity. In another embodiment, the outer coating 24 may be made of a 10 µm thick layer of parylene c and a 0.5 mm thick layer of gelatin. The gelatin, which can be soft, hard or vegetable gelatin, can be cross-linked to increase its durability. In this way, a device comprising an outer layer made of parylene c can be designed so that it undergoes a change in its dimensions at the desired speed. Of course, other dimensions and other suitable substances can be used.

The device 20 may have been manufactured in a manner that is similar to pharmaceutical tablets, pills or capsules, etc., by molding, pressure, extrusion and other methods. For example, the internal filler 22, which may include microspheres of a hydrophilic substance encapsulated within a fat-based matrix or within a coating of parylene c, can be pressed into a tablet approximately 11 mm thick and then , coated with a thin outer coating 24 (approximately 10 µm) which, in general, is not degradable under conditions inside the internal cavity (such as low pH, temperature, enzymatic degradation, etc.). When they are being used, the microspheres absorb liquids from the environment and swell, accumulating pressure that ultimately causes the outer coating 24 to break.

In an alternative embodiment, the osmosis of the internal filling can favor a diffusion of ions inside the internal body cavity, a gradual emptying of the inner core and a flow of liquids inside the device. The inner core that is emptied is exchanged for liquids, which exert pressure on the lining of the device, so that, after reaching a predetermined value, the outer lining is broken and the entire device dwarfs.

It should be appreciated that the device can comprise more than two layers, so that each layer has its own dynamics, as described above. On the other hand, it should be appreciated that the change in dimension of the device can be influenced by different parameters, such as the thickness of each layer, or by different properties of the manufacturing material of each layer, etc. A predetermined pressure that is suitable for breaking one of the coatings may not be suitable for breaking another coating. For example, different hydrogel fillers can be induced to undergo a swelling change. A thermosensitive hydrogel can be stimulated by a change in temperature to experience polymer-polymer and water-polymer interactions, which results in a change in the swelling of the hydrogel. In the same way, an acidic or basic hydrogel can be induced by a change in pH. The swelling of modified hydrogels can also be stimulated. For example, a hydrogel containing electron acceptor groups can be stimulated by the presence of electron donor compounds, a polyelectrolyte hydrogel will be stimulated in the presence of an applied magnetic field, and magnetic particles dispersed in microspheres, such as alginate microspheres, They will be stimulated in the presence of an applied magnetic field. In this way, a device according to an embodiment of the invention can be externally controlled; namely, the transition of the device from an initial phase to a final phase can be controlled, for example, by artificially modifying the

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temperature or pH inside the internal cavity, or by externally applying an electric or magnetic field to the internal body cavity.

External control of the transition of the device from an initial phase to a final phase can be useful in cases where the device is locked inside an internal body cavity that has an environment that does not favor the transition from an initial phase to a final phase. For example, the device may be blocked in the large intestine of a patient due to a stricture in the large intestine. The environment of the sinus of the internal cavity of the large intestine may sometimes not be sufficiently diluted to provide the predetermined pressure by a flow into endoluminal fluids. The transition of the device to its final dimensions can then be initiated externally, for example, as described above, in order to contribute to the decrease of the device.

It should be appreciated that the device according to an embodiment of the invention may be made of materials that are degradable by external methods, such as by ultrasound, in the event that an external operator wishes to decrease the device before the device is varied. to its final dimensions.

In Figure 2B, the device 200 comprises an outer liner 204 and an inner padding (not shown). The outer coating 204 is reinforced differently, that is, it has areas of different strengths. The device 200 may be shaped, for example, in the form of a capsule or otherwise shaped. The outer liner 204 and the inner padding may have been made of any suitable material, for example, as explained above. Certain specific areas of outer sheath 204 are weaker than neighboring areas, so that when pressure is exerted on these weaker areas, outer sheath 204 breaks or crushes in the vicinity of these areas. In the example illustrated in Figure 2B, a patch 212 located at one end of the device 200 or a band 214 around the middle part of the device 200 is weaker than the neighboring areas 212 ’and 214’. For example, patch 212 and / or band 214 may be thinner than neighboring areas and, therefore, will be more susceptible to pressure than neighboring areas 212 ’and 214’. Alternatively, patch 212 and / or band 214 may be more permeable to liquids than neighboring areas and, therefore, while within an internal body cavity, a greater flow of liquids from inside the internal cavity passes to through these areas than through the neighboring areas. This differential flow of liquids causes pressure to be exerted in the vicinity of the most permeable areas, thereby causing the outer coating 204 to break or crush in these areas. The differential permeability in these areas can be caused, for example, by the use of a thinner coating layer in these areas, by drilling holes 213 in these areas, by the use of different materials to manufacture the different areas, and in other ways

A device 200 may include an outer liner 204 and an inner fill consisting of a gas or liquid body. Alternatively, the device may include multiple layers: outer lining layers and inner filler layers, as described above. The pressure of a certain magnitude, exerted by the afferent or efferent flow of liquids or by the swelling of an inner core layer against the outer liner, causes the outer liner 204 to be broken by concrete weakened areas, such as by a patch 212 and / or along a band 214. In this way, the device 200, which has an outer liner 204 with areas of differential resistance, may have been designed to undergo a change of dimensions in a stepped manner, such that the Rupture of the outer lining, which can be carried out gradually, will cause an immediate change in the dimensions of the device 200.

In such an embodiment, during the initial phase, while the pressure inside the device is increasing, the outer coating is not affected by the increasing pressure or by the conditions inside the internal cavity (even if there is erosion of the outer coating during the initial phase , this will not usually be greater than about 5% of the initial dimensions of the outer covering) and, therefore, the shape and dimensions of the device are not significantly modified. However, once the predetermined pressure has been reached, the outer lining will be crushed or broken and the dimensions of the device will be reduced abruptly, or stepwise, or in an approximate manner to a stepwise manner. Thus, while both the outer coating and the inner padding can see their modified dimensions or dissolve gradually, the overall reaction is an approximation to a step function.

An approach to a step reaction according to an embodiment of the invention has been presented schematically in Figure 2C. The graph shown in Figure 2C, which represents the dissolution of a two-layer device according to one embodiment, includes two exponents represented as (a) and (b). The first exponent (a) represents an outer layer of essentially fixed dimensions (for example, with a change in dimensions of up to about 5% of the initial dimensions), while the second exponent (b) represents a voiding or dissolution of the inner layer The outer layer protects and prevents dissolution or emptying of the inner layer. However, once the outer layer has dissolved or broken, the process of dissolving or emptying the inner layer begins. The combination of the two exponents approximates the required step function.

A test device is not always easy to see when it is inside a person's body, and it may not be recognized when the device leaves the body, for example, in the case of a test device for the GI tract. A person who has swallowed or otherwise ingested the test capsule does not always know when, and

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With what dimensions, the test capsule has come out of your body. In one embodiment, a test capsule for the GI tract has been designed so that it remains with its initial dimensions, in live conditions, for approximately 100 hours or more. In alternative embodiments, other time limits may be used, and test devices may be designed for other internal body cavities, in accordance with the specific internal body cavity having specific and known anatomy and physiology.

In another embodiment of the invention, a monitoring mechanism is included that allows a user to externally track the progress of the test device or otherwise track the test device within the internal body cavity. The slowdown or blockage of the device within the internal body cavity for a period of time that is longer than the time it usually takes for a device to pass through an internal cavity of normal configuration, implies an abnormality of The internal body cavity. The position of the test device at a given time within an internal body cavity can be determined by known methods. In this way, clinical anomalies and / or conformation anomalies, such as the strictures in the GI tract, can be identified and located in specific areas of the internal body cavity.

In FIGS. 3A-3D, test devices according to some embodiment of the invention have been illustrated and exemplified. Referring to Figures 3A and 3B, the test device 40, which may have been designed and manufactured as explained above, includes, for example, a thin, semipermeable, speed limiting coating 401, such as a coating 10 mm thick C, a thicker shell 405 that confers mechanical stability, such as a layer of gelatin between 1 mm and 2 mm thick, a swallowable filling material 407, such as a layer of a hydrogel between 3 mm and 4 mm thick, and a monitoring device 43, which, in one embodiment, is approximately 3 mm wide. The device 40 is swallowed or otherwise inserted into the GI tract of the patient 300 and the patient 300 is then monitored when placed in the vicinity of a receiving system 305, as will be detailed further below.

The monitoring device 43 can be, for example, a passive ID tag that warns of its presence only by internal activation. Such an ID tag may be of a known construction that includes, for example, a processor (not shown), a transmitter (not shown) and an antenna (not shown) intended to receive power from an external transmission device 303. Such tags Passive miniature IDs are used, for example, as implantable tags for animal identification. Such implantable labels are manufactured by Tiris, Microchip and other companies.

In alternative embodiments, the tag may include other components; For example, the tag may include a Gunn diode instead of a processor. In another embodiment, the tag may include a passive acoustic element that will respond to external induction to create at least one acoustic signal, such as a click, a beep or a click. An external operator can induce the label to send an acoustic signal and can then listen to the signal by placing a stethoscope, for example, on the patient's body. Listening to the signal will indicate that the label is still on the patient's body. The operation of the tag can be coupled to the device in such a way that if the device has disintegrated, the tag will not respond by sending an acoustic signal. For example, a component of the tag, such as a battery to power the tag, can be attached to the device shell such that, once the device shell is broken or crushed, the battery will no longer be connected. to the tag and the tag will not be able to produce an acoustic signal.

In another embodiment, the monitoring device 43 has been magnetized to obtain a net magnetic dipole moment. Once the device 410 has been introduced live, its magnetic field distribution in the internal body cavity can be recorded for several time intervals with a receiver system 305 (for example, a magnetometer) and, at each instant of time, it can calculate the position of the device inside the internal body cavity from the measured field distribution, assuming a magnetic dipole model.

Optionally, the monitoring device 43 can be active, such as a beacon that emits signals continuously or periodically to an external receiver system 305 that warns of its presence. In one embodiment, the monitoring device 43 is an acoustic beacon. The acoustic beacon, according to an embodiment of the invention, generates at least one acoustic signal. According to another embodiment, the acoustic beacon includes an electronic circuit that produces a periodic impulse (for example, every 15-30 seconds). The circuit is connected to an acoustic element, such as a buzzer, a clicker, a whistle, etc., for example, through an electroacoustic converter, such that an acoustic signal is periodically generated.

In one embodiment, the monitoring device 43 is energetically powered by a Power PaperTM power supply, provided by the Power Paper Ltd. of Israel. Preferably, the battery can last more than 200 hours. The monitoring device 43 can be operated by a read relay switch. The switch can be switched to an ON or OFF position by distancing an external magnet from the monitoring device 43, as is known in the art. Thus, for example, the device 40, which includes a monitoring device 43, such as an acoustic beacon, can be packaged in a magnetic package. The acoustic beacon is deactivated while it is still in the magnetic package. Once the device 40 is released from the packing, usually just before inserting the device 40 live, the monitoring device 43 is activated. In another embodiment, the acoustic beacon can only be activated.

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after the device 40 has broken or disintegrated.

An external operator can, at any time after the device 40 has been inserted live, listen to the acoustic signal by any known means, for example, by placing a stethoscope on the patient's body. The fact of hearing the signal indicates that the label is still inside the patient's body. The approximate position of the monitoring device can be inferred. In an alternative embodiment, the signals from the monitoring device 43 are received by the receiving system 305 and the position of the monitoring device 43 can be calculated by known triangulation methods. The calculations, according to an embodiment of the invention, are carried out in a processing unit 408. In this way, the monitoring device 43 can be monitored and its position can be known while being inside the patient's body 300 and when it leaves the patient's body.

The monitoring device 43, usually a miniature device, has been shaped and sized so that it can pass itself freely through an internal body cavity, even if the internal body cavity is constricted or narrowed, or another mode set abnormally. In such a case, the device 40 is broken or crushed, or otherwise altered as described above, and the device 40, dwarfed, and the monitoring device 43 freely passes through the internal body cavity to exit the body. of the patient.

Referring to Figures 3C and 3D, a test device 400 of one embodiment comprises an outer liner 404 and an inner pad 402. The outer shell 404 and the inner pad 402 may have been manufactured as described above. The internal filler 402, which may be a filler material, may additionally comprise a marker 403. In one embodiment, the label is a radiopaque material, such as barium sulfate, or other detectable material, such that the device Test 400 can be seen by X-rays or other detection methods. In an alternative embodiment, the marker is a pigment, which can be dispersed or incorporated into the filling. In yet another embodiment, the label is magnetite (Fe3O4), for example, magnetite powder in poly (methyl methacrylate). In this case, the device 400 is magnetized to obtain a net magnetic dipole moment such that the device 400 can be monitored as described with reference to Figures 3A and 3B. On the other hand, in yet another embodiment, the marker is a radioactive marker. In another embodiment, the marker can be a chemical that can interact with the patient's body to achieve a sensation that is perceived by the patient. For example, niacin, when allowed to interact with the patient's body, can cause a certain sensation, indicating to the patient that niacin has been released inside his body.

The device 400 is inserted into the GI tract of a patient 300 and can be monitored by an appropriate detector 301, for example, an X-ray machine, a gamma camera or a magnetometer. The detector 301 is usually displaced along the body of the patient 300 and, using a plurality of detectors or receivers (not shown) and a processing unit 302, can detect and calculate, by known methods, the position of the marker 403.

Typically, when the device 400 reaches its final dimensions, the outer liner 404 dissolves or breaks and the inner pad 402 and any scattered or incorporated markers 403 are released into the body's internal cavity. Therefore, according to one embodiment, a patient 300 or an external operator can be notified of the fact that the device 400 has reached its final dimensions by a sudden sensation, for example, or by the appearance of a marker in the content or excretions of the internal body cavity, for example, by the appearance of colored feces, etc. In another embodiment of the invention, a marker 403 may be used to indicate the position of a constraint or other configuration anomaly. Marker 403, which can be a pigment, can be dispersed or incorporated into the inner filling, or be contained in a separate layer under the coating 404, so as to be exposed when the outer coating 404 dissolves or breaks. In this way, a marker can be left inside an internal cavity, in the position of an abnormal configuration of that internal cavity (such as in the position of a stricture) and can, accordingly, mark the position. In one embodiment, a subject may swallow a device according to an embodiment of the invention, in order to study the GI tract. In the case of a strictness, the device will be delayed in the stricture and, finally, it will undergo a change of dimensions, as described above, releasing a marker in the place of the stricture. A surgeon will then be able to identify the position of the stricture by externally observing the GI tract and detecting the marker. The procedure for eliminating a restriction, for example, in the GI tract can thus be facilitated. In another embodiment, the device may also include a tag such as the tags described above, to help locate the device.

In some embodiments, it may be preferable that the marker is long lasting (for example, a few days) and visible through the tissues of the internal cavity, so that it is detectable from the outside of the internal cavity. Examples of such markers may be Indian ink or known metal markers. Also, particularly for use in the GI tract, markers that can be erased, such as food coloring, can be used.

In a further embodiment, the marker can be sprayed on the outside of the device, for example, by means of

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production of high pressure in the layer containing the marker, such that, when this layer is exposed, its content is propelled by force from the device onto the tissue of the surrounding internal cavity. Other methods may be possible to forcefully propel the marker from the device, such as the use of an injection mechanism in the device, which is activated when the outer coating dissolves or breaks.

According to another embodiment, as long as the outer coating 404 remains intact and the marker 403 is enclosed within the outer coating 404, the marker 403 will be detectable by the detector 301. If the outer coating 404 dissolves or breaks, the internal filler 402 and any marker 403 dispersed or incorporated therein will be released into the internal body cavity and dispersed in such a way that marker 403 will no longer be detectable by detector 301. Consequently, test device 400 it can be monitored while having its initial dimensions, by using the detector 301. Once the device 400 reaches its final dimensions, the marker 403 will be dispersed and undetectable by the detector 301. Therefore, the device can be tracked 400 and its position, while in the initial phase, can be calculated. In the final phase, the filling will be dispersed to the interior environment of the internal body cavity, so that the typical signal of the initial phase will no longer exist. The device 400 may also contain a monitoring device, such as the monitoring device 43 (Figure 3A), for additional monitoring once the device 400 reaches its final dimensions.

Additionally, the monitoring device 43 can also serve as a platform for additional live detection units, such as a pH meter, a thermometer, an imaging device, a pressure detector, etc. Detection units can transmit data, wirelessly or not, to an external receiving system while traversing the internal body cavity. Optionally, the devices according to embodiments of the invention may comprise, as before, a miniature live detection unit, which is not connected to the monitoring device 43.

According to one embodiment, a live imaging device, such as the device described in WO 01/65995 (incorporated herein by reference), may include an electronic tag, such as an RFID [radiofrequency identification ]. An imaging device, according to one embodiment, may include an electronic tag, an image sensor, a lighting source and an internal power supply source, such as a battery. The imaging device may also include a transmitter to transmit image data to an external receiving system.

Reference is now made to Figure 4, which schematically illustrates an examination device according to an embodiment of the invention. The device 50 has a body 58 and a cover 58 ’which are usually, but not necessarily, made of different materials. The body 58 and the cover 58 'enclose an interior space that usually contains a filling material 52 and an ID tag 53. The body 58 and the cover 58' are coated with a thin coating layer 54, except in a window 56. In window 56, the cover 58 'can be exposed and come directly into contact with an environment of the internal body cavity. According to one embodiment, the device 50 can be assembled by fixing (for example, by gluing) a body filled with the filler material and the ID tag to a cover having a projection 56 ’. The body 58 filled with the filling material 52, together with the cover 58 'containing the projection 56' fixed thereto, are then coated with the coating layer 54. The projection 56 'is then cut and removed near the cover 58 ', leaving a window 56 that is not coated with the coating layer 54.

The device 50 can be inserted into the GI tract and can be driven through the GI tract by, for example, peristaltic movements, as described above. The coating layer 54 is usually impervious to liquids from the GI tract, while the cover 58 ′ is usually permeable to liquids from the GI tract. The surrounding liquids can, therefore, enter through the window 56, which is not protected by the coating layer 54. The liquids from the GI tract will diffuse or flow into the interior through the window 56, thereby dissolving the cover 58 ', at a speed that can be dependent on parameters such as the size of the window 56, the properties of the manufacturing material of the cover 58' and the thickness of the cover 58 '. After a predetermined time, the cover 58 'will dissolve sufficiently to create an opening through the window 56, through which the liquids of the GI tract can come into contact with the body 58, and through which the filling material 52 and, ultimately, ID tag 53 may leave the device. The body 58 is usually made of a material that is faster to dissolve than the material with which the lid 58 'has been manufactured. Therefore, once an opening in the lid 58 ’has been created, the device 50 will quickly empty its contents, leaving only a coating layer 54 empty.

A device according to an embodiment of the invention can be made, for example, of a jelly body and a wax lid. Other materials can be used, the device can be filled with powdered sugar, into which a 12mm x 2mm RFID tag (or other appropriate beacon or identification device) is inserted glass coated. The filled body and the lid can be coated with, for example, a layer between 8 µm and 10 µm of parylene c. In alternative embodiments, the lid may be made, for example, of a lipophilic material of vegetable or hydrocarbon origin (simple and / or complex). According to an embodiment of the invention, the lid can be made essentially of a hydrophilic material, for example, wax. According to one embodiment, the hydrophobic material may comprise microparticles to facilitate the flow of body fluids to the

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inside the lid and to facilitate the disintegration of the lid. A system that may be suitable for use in an embodiment of the present invention may be a nanoparticle system, for example, formed by a solid hydrophobic inner core and a cationic exterior. The nanoparticles can be encapsulated within microcapsules. In one embodiment, the nanoparticles can be encapsulated within moisture sensitive microcapsules. Such systems are manufactured, for example, by Salvona, USA. The device can be filled, for example, with powdered sugar or other excipients. Barium or other suitable materials can be mixed into the filling for easy monitoring of the device by X-rays. Alternatively, the device may not need a filling, which is usually intended to confer mechanical resistance to the device. For example, the gelatin body may be thick enough to confer the required mechanical strength, without having to be filled with a powder filling. The device containing the ID tag can be monitored by using a reader such as a suitable reader provided by Trovan Ltd. of the UK. The tag can be like the tags described herein, such as a radioactive marker, a magnetic device

or a radio based tag.

In an alternative embodiment, a device, according to an embodiment of the invention, can be used for the controlled release of substances into an internal body cavity, such as the GI tract. According to an embodiment of the invention, substances such as an active agent, a medicament or markers can be included in a component or compartment of the device, in order to be released into an internal body cavity. In one embodiment, the substances can be released in a specific place, usually in a place of an abnormal configuration, such as a stricture. According to one embodiment, the filler material 52 may include medicaments specifically intended to treat a constricted or constipated GI tract. Such medications may include, for example, steroids. For example, one or more active agents in powder form may be mixed with any suitable filler material, for example, as described above. According to another embodiment, one or more active agents can be included in a nanoparticle that is microencapsulated in the cap 58 ’. In yet another embodiment, one or more active agents may be incorporated into the body 58. The active agents may be soluble in the components of the cap 58 'or the body 58, or the active agents may be dispersed within a solid matrix , for example, in the material comprising the body 58 or in the nanoparticles that are included in the cap 58 '. Similarly, a marker, as explained above, can be incorporated into components of a device according to an embodiment of the invention. Medications or other substances can be inserted into the device in the form of a tablet, a gel or a fluid. According to one embodiment, a liquid solution containing a substance may consist of an oily solution that does not dissolve the body of gelatin. The incorporation of substances, such as active agents or markers, into components of the device, according to embodiments of the invention, can be carried out by any suitable method known in the art, for example, as is known in the art. pharmaceutical field

A device according to an embodiment of the invention is usually disintegrated and its contents released after a predetermined period of time, for example, after 100 hours or more. On the other hand, a device according to an embodiment of the invention is detained in an abnormal internal cavity in a clinical sense.

or of configuration, so that it disintegrates and its contents are released substantially only within an abnormal internal cavity from a clinical or configuration point of view, for example, in the place of a stricture or in a constricted GI tract. In this way, medications or markers that are specifically intended to treat or mark strictures or other abnormalities of configuration of an internal body cavity, or active agents specifically intended to treat motility abnormalities, such as constipation, can be released, from according to embodiments of the invention, in a specific way as to its location, for the specific treatment of the anomaly.

According to one embodiment, a GI tract suspected of being constricted can be studied by ingesting a device according to an embodiment of the invention. According to one embodiment, the device disintegrates after a period of 12 or 24 hours. A patient suffering from a bowel with acute stricture may show symptoms 12 or 14 hours after ingesting the bolus with the device. In this case, the patient is usually operated immediately. The device according to an embodiment of the invention may comprise a marker, such that the constricted site is marked shortly before the surgical procedure, directing the surgeon immediately to that place. In yet another embodiment, the device may comprise such a medicine, that the place of the stricture can receive medical treatment just before the surgical procedure.

It will be appreciated by those skilled in the art that the present invention is not limited by what has been shown and specifically described hereinbefore. Instead, the scope of the invention is defined by the following claims.

Claims (4)

E02745775 10-09-2014 1.-A system to indicate the transferability of a target device, live, non-degradable, through a GI tract, so that the system comprises: - a target device, live, not degradable; 5 - a live device (50), comprising:

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a soluble body (58);

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a soluble cover (58 ’), fixed to the body (58), such that said body (58) and said cover (58’) define a closed receptacle;

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 an outer coating (54), which is essentially impervious to liquids from the GI tract, which

10 encloses the lid (58 ') and the body (58) with the exception of a window (56), such that said lining (54) covers less than the entire lid (58'), so that the lid (58 ') is not coated in the window (56); Y - a passive monitoring device (53), said device having live (50) initial dimensions similar to the dimensions of the target device, live, not degradable, such that the body (58) is made of a material that is faster to dissolve than the material of the lid (58 ’); and in which the dissolution rate of the lid (58 '), once it has come into contact with the liquids of the GI tract, depends on parameters of the window size (56), the properties of the material of the lid 20 (58 ') and the thickness of the lid (58'), so that a predetermined period of time, after which the lid (58 ') will dissolve sufficiently to create an opening through the window (56) , through which the liquids of the GI tract come into contact with the body (58), depends on the material and the thickness of the lid (58 ') as well as the size of the window (56), so that the lid (58 ') is of such material and thickness, and the window (56) is of a size such that the body (58) and the lid (58') dissolve in liquids 25 of the GI tract at such a speed that:

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the live device (50) has its initial dimensions during the period of contact time with the liquids of the GI tract; Y

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 after the predetermined period of contact with the liquids of the GI tract, the dimensions of

said live device (50) are reduced to final dimensions that are smaller than the initial 30 dimensions; Y - an external inductor for inducing said monitoring device (53) to send a signal. 2. The system according to claim 1, wherein the monitoring device (53) is an electronic ID tag, a magnetized device or an acoustic device. 3. The system according to claim 1, wherein the outer coating (54) includes a material or a combination of materials selected from the group consisting of: parylene c, hard gelatin, soft gelatin, vegetable gelatin and a hydrogel 4. The system according to claim 1, wherein the live device additionally comprises a substance enclosed within the closed receptacle. The system according to claim 4, wherein the substance consists of one or more of: a medicament, a filler material, a biodegradable polymer, microparticles of a hydrophilic substance, a hydrogel, powdered sugar and / or barium. 6. The system according to claim 1, wherein the predetermined period of time is a period of one hundred hours or more. The system according to claim 1, wherein the initial dimensions comprise a diameter between 1 mm and 12 mm, and in which the final dimensions comprise a diameter between 2 µm and 10 µm. 13